Josef Rieder

Mass spectrometric profile of exhaled breath—field study by PTR-MS

Recently, increased interest has focused on the diagnostic potential of volatile organic compounds (VOC) exhaled in human breath as this substance group has been conjectured in indoor air quality and disease screening. Proton transfer reaction-mass spectrometry (PTR-MS) has been established as a new tool for a rapid determination of exhaled air profile. However, no investigations have been carried out into the profile of exhaled air as determined by PTR-MS. Therefore, it was the aim of the present study to determine the profile of exhaled breath in a field survey enrolling 344 persons. Analysis was performed using PTR-MS. No significant correlations with age, blood pressure, and body mass index could be observed with any molecular mass. The present study delineates possible reference values for PTR-MS investigations into exhaled air profile. In conclusion, the present study was the first to delineate mass spectrometric characteristics of an average patient sample as possible reference values.

Inducible nitric oxide synthase--time for reappraisal.

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid L-arginine. iNOS-derived NO plays an important role in numerous physiological and pathophysiological conditions, e.g. blood pressure regulation, inflammation, infection, and the onset and progression of malignant diseases. iNOS has been conjectured both as a marker and a therapeutic target in these situations. iNOS is a mediator of unspecific host defence, central in the clearance of bacterial, viral, fungal and parasitic infections. However, excess production of NO appears to be linked to tissue damage and organ dysfunction, e.g. the hypotensive and vasoplegic state characteristic for septic shock. However, the use of iNOS-inhibitors in septic patients should be performed carefully with regard to the essential functions and properties of NO in blood pressure/blood flow regulation. Considering iNOS-derived NO as a multifactorial transmitter of tumorigenesis and tumor progression, it is tempting to speculate on therapeutical interference with iNOS activity, especially in tumors where metastatic activity, host denfence mechanisms and the level of differentiation seem to be correlated to iNOS expression. It is the aim of this review to provide basic insights into the NOS family of enzymes as well as their regulation. In the second part of the review, we will point out the pivotal roles NOS play in inflammation and neoplastic diseases.

Cervical and High Thoracic Ligamentum Flavum Frequently Fails to Fuse in the Midline

Background Cervical and high thoracic epidural anesthesia and analgesia have gained increasing importance in the treatment of painful conditions and as components of anesthetics for cardiac and breast surgery. In contrast to the hanging-drop technique, the loss-of-resistance technique is thought to rely on the penetration of the ligamentum flavum. However, the exact morphology of the ligamentum flavum at different vertebral levels remains controversial. Therefore, the aim of this study was to investigate the incidence and morphology of cervical and high thoracic ligamentum flavum mid-line gaps in embalmed cadavers. Methods Vertebral column specimens were obtained from 52 human cadavers. On each dissected level, ligamentum flavum mid-line gaps were recorded and evaluated with respect to shape and size. Results The following variations were encountered: complete fusion in the mid-line, mid-line fusion with a gap in the caudal part, mid-line gap, and mid-line gap with widened caudal end. The incidence of mid-line gaps at the following levels was: C3–C4: 66%, C4–C5: 58%, C5–C6: 74%, C6–C7: 64%, C7–T1: 51%, Th1–Th2: 21%, Th2–Th3: 11%, Th3–Th4: 4%, Th4–Th5: 2%, and Th5–Th6: 2%. The mean width of mid-line gaps was 1.0 ± 0.3 mm. Conclusions In conclusion, the present study shows that gaps in the ligamenta flava are frequent at cervical and high thoracic levels but become rare at the T3/T4 level and below, such that one cannot always rely on the ligamentum flavum as a perceptible barrier to epidural needle placement at these levels.

Analysing ventricular fibrillation ECG-signals and predicting defibrillation success during cardiopulmonary resuscitation employing N(α)-histograms

Mean fibrillation frequency may predict defibrillation success during cardiopulmonary resuscitation (CPR). N(alpha)-histogram analysis should be investigated as an alternative. After 4 min of cardiac arrest, and 3 versus 8 min of CPR, 25 pigs received either vasopressin or epinephrine (0.4, 0.4, and 0.8 U/kg vasopressin versus 45, 45, and 200 microg/kg epinephrine) every 5 min with defibrillation at 22 min. Before defibrillation, the N(alpha)-parameter histogramstart/histogramwidth and the mean fibrillation frequency in resuscitated versus non-resuscitated pigs were 2.9+/-0.4 versus 1.7+/-0.5 (P=0.0000005); and 9.5+/-1.7 versus 6.9+/-0.7 (P=0.0003). During the last minute prior to defibrillation, histogramstart/histogramwidth of > or =2.3 versus mean fibrillation frequency > or =8 Hz predicted successful defibrillation with subsequent return of a spontaneous circulation for more than 60 min with sensitivity, specificity, positive predictive value and negative predictive value of 94 versus 82%, 96 versus 89%, 98 versus 93% and 90 versus 74%, respectively. We conclude, that N(alpha)-analysis was superior to mean fibrillation frequency analysis during CPR in predicting defibrillation success, and distinction between vasopressin versus epinephrine effects.

Accuracy in estimating the correct intervertebral space level during lumbar, thoracic and cervical epidural anaesthesia

Background:  Even in the absence of factors concealing anatomical landmarks, high failure rates in correctly determining a given lumbar interspace have been reported.

Gender and age specific differences in exhaled isoprene levels.

The analysis of volatile organic compounds (VOC) in the human breath has attracted a considerable amount of clinical and scientific interest during the last decade. In our study, we turned our attention to gender and age specific differences of exhaled volatile compounds, particularly on isoprene which is one of the most abundant organic molecules found in human exhaled air. A total of 126 test persons were enrolled in the study: 66 females and 60 males. Moreover, the participants were classified into six groups with regard to their age. In a standardized setting all of them had to exhale the endexpiratory breath into a sample bag. The volatile compounds at m/z values from 21 to 229 were analyzed by using proton-transfer-reaction-mass-spectrometry. Isoprene (at m/z 69) was found to be highly significantly (p<0.001) elevated in the exhaled air of male subjects. Furthermore, it could be shown that 19-29 years old subjects exhale significantly lower levels of isoprene than older adults (p=0.002). No significant differences between groups were detected for any other measured mass. In conclusion, the present study demonstrates gender and age specific differences of isoprene levels in the exhaled air. These findings may be of potential clinical relevance regarding the multifaceted roles of isoprene, representing both indicator and effector molecule.

NEOPTERIN INDUCES NITRIC OXIDE-DEPENDENT APOPTOSIS IN RAT VASCULAR SMOOTH MUSCLE CELLS

Numerous studies indicate that proinflammatory substances like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) as well as macrophage-derived neopterin are increased in atherosclerotic tissue and thus are potentially involved in the process of atherogenesis. Since apoptotic death of vascular smooth muscle cells (VSMC) is reported to occur in atherosclerotic lesions, we investigated the effects of neopterin, TNF-alpha, and IFN-gamma on apoptosis in cultured VSMC. Morphological changes characteristic of apoptosis as well as DNA fragmentation were detected in cells treated with neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma. Simultaneously, neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma led to inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) synthesis. NO generation was significantly reduced when cells were cotreated with the competitive iNOS inhibitor aminoguanidine. This was accompanied by decreased percentual apoptosis as detected by FACS analysis using all kinds of stimuli. We conclude that neopterin as well as TNF-alpha/IFN-gamma are potent mediators of apoptotic death in VSMC which is at least in part triggered by NO synthesis induced by these proinflammatory mediators.

Online monitoring of air quality at the postanesthetic care unit by proton-transfer-reaction mass spectrometry.

The subthreshold exposure to trace anesthetic gases is not associated with considerable risk of adverse health effects. Online control of ambient air exchange at the postoperative workplace may help in supervising air quality and lead to cost reduction. A proton-transfer-reaction mass spectrometer system was used for online monitoring of volatile organic compounds, especially anesthetic gases. The mean exposure to sevoflurane and isoflurane at the urological postanesthesia care unit (PACU) was 15.9 and 9.5 parts per billion, respectively. Sevoflurane and isoflurane concentrations at the urological PACU showed a patient turnover-dependent burden during our investigation period. Because modern PACUs have a high ventilation capacity, the 24-h occupational burden by anesthetic gases at the PACU is relatively low. Monitoring and controlling of ambient air by automatic built-in alarm systems would be useful for quality control of the postoperative workplace. Moreover, energy costs of ventilation systems could be reduced by coupling ventilation capacity to the effective exposure.

Sevoflurane in exhaled air of operating room personnel.

Evidence on potential health hazards arising from exposure to volatile anesthetics remains controversial. Exposure may, in principle, be supervised by monitoring of ambient air or, alternatively, in vivo. We used the Proton Transfer Reaction-Mass Spectrometry to screen the breath of 40 operating room staff members before operating room duty, 0, 1, 2, and 3 h after duty, and before commencing duty on the consecutive day, and control persons. Staff members exhibited significantly increased sevoflurane levels in exhaled air after duty, with a mean of 0.80 parts per billion as compared with baseline values of 0.26 parts per billion (P < 0.05). Analysis of variance with adjustment for within correlation (repeated measurements) showed a statistically significant time-effect (P < 0.001). We conclude that (a) Proton Transfer Reaction-Mass Spectrometry biomonitoring of exhaled sevoflurane can serve as a simple and rapid method to determine volatile anesthetic excretion after occupational exposure, and (b) significant concentrations of sevoflurane may be continuously present in persons exposed to sevoflurane on a daily basis.

Neopterin–Induced Tumor Necrosis Factor–· Synthesis in Vascular Smooth Muscle Cells in vitro

Synthesis and secretion of proinflammatory mediators like tumor necrosis factor–α and neopterin are common events in severe systemic inflammatory disorders, e.g. sepsis and septic shock. Recent data suggest that both substances show similarities with respect to their bioactivities. In the present study we investigated the potential interactions of neopterin and tumor necrosis factor–α on inducible nitric oxide synthase gene expression and nitric oxide generation in rat vascular smooth muscle cells. In addition, we studied the influence of neopterin on tumor necrosis factor–α synthesis in this cell type. Single stimulation of smooth muscle cells with either neopterin or tumor necrosis factor–α caused inducible nitric oxide synthase gene expression and nitric oxide production. Coincubation of cells with both compounds resulted in at least additive effects on nitric oxide synthesis. Quantification of tumor necrosis factor–α cDNA revealed a dose–dependent effect of neopterin on tumor necrosis factor–α gene expression. Similar results were obtained concerning the detection of tumor necrosis factor–α protein and the assessment of tumor necrosis factor–α bioactivity. These data suggest that neopterin and tumor necrosis factor–α are closely associated with regard to synthesis and effects, respectively. The interactions of both inflammatory mediators in vascular smooth muscle cells might contribute to the excessive release of nitric oxide observed during sepsis, thus triggering cellular destruction and multiple organ failure.